This application entitled "Multimodality Optical Imaging Tools for Cocaine Studies" will address the broad Challenge Area (06: Enabling Technologies) and Specific Challenge topic (06-DA-102: Tool Development for the Neurosciences). The central goal of this proposal is to develop novel imaging tools that will provide new insights into the cascading events resulting from chronic cocaine exposure, in particular, the toxic effects on cortical and subcortical brain regions and including neurovascular changes. One of the big challenges when imaging the responses of the rodent brain to drugs (i.e., cocaine) has been to distinguish vascular from neuronal effects. We recently developed and tested a novel dual wavelength laser speckle imaging (DWLSI) tool that enables, for the first time, simultaneous measurements of cerebral blood flow (CBF), blood volume and tissue hemoglobin oxygenation, which serves as marker of tissue activity at high spatiotemporal resolutions (30[unreadable]m, 10Hz) and over a relatively large field of view (FOV, 4x5mm2). Moreover, by co-registering with digital-frequency-ramping optical coherence tomography (DOCT) we can obtain an in vivo quantitative 3D image of the CBF network. In parallel we also developed intracellular calcium imaging using Rhod2-fluorescence technique, which serves as a marker of neuronal activity. In this Challenge Grant, we propose to develop a multimodality simultaneous imaging platform by combining DWLSI, DOCT and calcium fluorescence imaging to study the effects of acute and chronic cocaine exposures on rodent brain. By further integrating this technique with our micro relay lens (F300[unreadable]mx24mm), we will be able, for the first time, to expand our multimodality imaging capabilities to study cocaine effects in deep brain regions in vivo. The Specific Aims are: (1) to develop multimodality imaging platform to study cocaine effects on cortical brain;(2) to develop microprobe-based multimodality imaging platform for subcortical brain imaging. Successful development and validation of the proposed multimodality optical techniques will permit simultaneous imaging of vascular and cellular functions and their real-time responses to cocaine challenge in cortical and subcortical brain in vivo, thus enabling distinction and detailed study of neuronal and vascular changes. These proposed technological developments will have significantly impact on the biomedical imaging, neuroscience and drug abuse and translational research communities. In addition, Challenge grant funds for this project will create 3 research positions for 1 postdoctoral fellow and 2 graduate student, which will accelerate the pace of new imaging technology development and enhance the academic education for next generation on biomedical engineering and physics to bridge instrumentation development for neuroscience to translational research on drug abuse and addiction. PUBLIC HEALTH RELEVANCE: This application entitled "Multimodality Optical Imaging Tools for Cocaine Studies" will address the broad Challenge Area (06: Enabling Technologies) and specific Challenge topic (06-DA-102: Tool Development for the Neurosciences). The central goal of this proposal is to develop novel imaging tools that will provide new insights into the cascading events resulting from chronic cocaine exposure, in particular, the toxic effects on cortical and subcortical brain regions and including neurovascular changes. In this Challenge Grant, we propose to develop a multimodality simultaneous imaging platform by combining DWLSI, DOCT and calcium fluorescence imaging to study the effects of acute and chronic cocaine exposures to the rodent brain. In addition, by integrating this technique with our micro relay lens we will be able to expand our imaging capabilities to study cocaine effects in deep brain regions in vivo. Successful development and validation of the proposed techniques will permit simultaneous imaging of vascular and cellular functions and their real-time responses to cocaine challenge in cortical and subcortical brain in vivo, thus enabling distinction and detailed study of neuronal and vascular changes. The proposed technological developments will have significantly impact on the biomedical imaging, neuroscience and drug abuse and translational research communities. In addition, Challenge grant funds for this project will create 3 research positions for post-doctor fellow and graduate students, which will enhance the academic education for next generation on Biomedical Engineering and Physics to bridge instrumentation development for neuroscience to translational research on drug abuse and addiction.